The objectives of the proposed research are to investigate the mechanisms involved in intestinal adaptation after the ileum and or jejunum are subjected to various stimuli and in the regulation or control of intestinal cell proliferation. The responses of portions of the intestine to a number of stimuli including X-irradiation and resection will be documented and quantified. The magnitude, the time of earliest appearance, and the persistence of change will be studied not only in the intestinal region most directly affected by the treatment employed, but also in more remote untreated sites of the gastrointestinal tract. The parameters of the intestinal response to be measured include determination of cAMP levels, crypt depth, villus height, labeling index, crypt cell migration rate, cell generation time, and tritiated thymidine uptake per crypt or per mg of intestine. The dependence of crypt size and cell production rate on villus number and size will also be assessed when feasible. Even though it has not been possible in our hands to detect a humoral factor after resection or X-irradiation of the intestine, it may exist. Accordingly, electrophoretic analyses of tissue homogenate and blood sera will be made. If it is possible to implicate humoral factors in the control of cell proliferation and migration, then attempts will be made utilizing techniques of protein separation, to purify such substances and to determine their chemical properties. The objective would then be to use these substances to obtain antisera which could be suitably labeled and reinjected in attempts to elucidate sites of production and possible modes of action.